1. Field of the Invention
The present invention relates to a method of surface modification to create areas resistant to the adsorption of biomolecules and the patterned and unpatterned surfaces obtained by this method.
2. Discussion of the Background
Biosensor technology has opened the doors for the incorporation of a wide variety of organic molecules, particularly proteins, into optical and electronic devices. In addition, there is increasing recognition of the potential for integrating organic molecules, including biomolecules and biomimetics, into optoelectronic hardware for improved speed, memory, signal transition, and miniaturization. As more complex devices are envisioned, these relatively large molecules must be selectively attached to surfaces such as glass and silicon. Previous methods used for patterning of biomolecules on surfaces include ink jet printing, standard microlithography followed by etching or lift off to remove preattached proteins, and attachment to photoactivated regions of a film. The first two methods are laborious, slow, and tend to damage the biomolecules. The last method is problematic in that most biomolecules are relatively sticky and will adsorb to the nonactivated regions of a silane film as well as to the activated regions.
Lowe et al, U.S. Pat. No. 4,562,157, describe patterns of covalently attached biomolecules deposited on photoactivated portions of a silane film. However, the disclosed method does not overcome the problem of nonspecific attachment of biomolecules to unmodified portions of the silane film.
Schoen, P. E. et al, 12th Annual Meeting of the IEEE, Nov. 1-6, 1990, describe the deposition of proteins using thiol silane films and subsequent pattern generation using photolithography. However, the disclosed method does not overcome the difficulties of maintaining protein activity during the photolithography.
J. H. McAlear et al, U.S. Pat. Nos. 4,103,064 and 4,103,073 disclose the attachment of thick films of proteins and subsequent microlithographic patterning using standard resist technology. The drawbacks of this method include: (1) many steps are involved; (2) there is no covalent attachment between the protein and the substrate; (3) many resists entail the use of organic solvents such as diglyme that are known to denature proteins; (4) the development of many resists require the use of alkaline developers which may denature proteins; (5) the crosslinking agent glutaraldehyde is known to denature proteins; and (6) exposure of the protein to harmful radiation.
Bhatia, S. K. et al, Anal. Biochem, 178, 408-413, 1989, describes the chemistry used for covalent attachment of biomolecules to a surface, utilizing heterobifunctional crosslinkers coupled to thiol silanes. This work does not demonstrate patterning of biomolecules.
A number of silane coating agents are known to reduce biomolecule adsorption (see: U.S. Pat. No. 3,746,196; and Arkles et al, in "Silylated Surfaces" D. Leyden, ed Gordon & Breach, N.Y. (1980)).
Thus, there remains a need for a method of modifying surfaces to create areas which are resistant to the adsorption of biomolecules. There also remains a need for a method of producing surfaces which contain a patterned area or areas which are resistant to the adsorption of biomolecules. There also remains a need for surfaces produced by such methods. There also remains a need for a method for preparing patterned surfaces having areas which exhibit a reduced capacity to react with heterobifunctional crosslinking agents.